背景:严重急性呼吸综合征相关冠状病毒2(SARS-CoV-2)病毒对间质性肺病(ILD)患者的影响仍然知之甚少。由于ILD患者通常有严重的潜在肺实质受累,免疫抑制疗法在这个人群中很常见,他们被认为是2019年严重冠状病毒病(COVID-19)肺炎的高危人群。我们的目的是探索SARS-CoV-2病毒检测呈阳性的ILD患者与未检测过的ILD患者之间的人口统计学和临床差异。
方法:在这项回顾性队列研究中,我们确定了成年人,2020年在芝加哥大学评估的未接种疫苗的患者被纳入ILD注册,并按SARS-CoV-2血清阳性状态分层。然后,我们比较了SARS-CoV-2血清阳性和SARS-CoV-2血清阴性患者之间的基线临床特征,并评估了自ILD诊断以来患者可能一直在进行的免疫抑制治疗。与基线ILD评估时间和肺功能测试相比,在COVID诊断时评估C反应蛋白和白细胞亚群。变量比较通过双侧t检验或卡方检验确定,使用具有最大似然估计的广义线性模型,拟合了logistic回归模型,以评估COVID-19的死亡几率.
结果:在我们队列中的309名ILD患者中,6.8%(n=21)的SARS-CoV-2检测呈阳性。SARS-CoV-2阳性者年龄较小(57岁vs66岁;P=0.002),基线总肺活量较高(81%vs73%,P=0.045),相似的强迫肺活量(71%vs.67%,P=0.37),和类似的一氧化碳扩散能力(71%vs.62%,P=0.10)在基线。在ILD和COVID-19患者中,67%接受过免疫抑制治疗,而没有COVID-19的ILD患者中,这一比例为74%。那些患有ILD和COVID-19的人也更有可能被诊断为自身免疫相关ILD(结缔组织病-ILD或具有自身免疫特征的间质性肺炎)(62%vs38%,P=0.029)。总的来说,在未接种自身免疫相关ILD的COVID-19患者中,死亡风险最高(OR=9.6,95%CI=1.7~54.0;P=0.01).
结论:SARS-CoV-2在ILD中普遍存在,可能会让未接种疫苗的年轻人,自身免疫性ILD,和免疫抑制治疗的风险更高。这表明需要对这组COVID-19高危患者进行COVID-19疫苗接种和治疗(住院和门诊)。需要更大规模的研究来全面探讨ILD与COVID-19免疫抑制治疗之间的关系。
BACKGROUND: The impact of the severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) virus on patients with interstitial lung disease (ILD) remains poorly understood. As patients with ILD often have severe underlying lung parenchymal involvement, and immunosuppressive therapy is common in this population, they are presumed to be at high risk for severe coronavirus disease 2019 (COVID-19) pneumonitis. Our aim was to explore demographic and clinical differences between those with ILD who tested positive for the SARS-CoV-2 virus compared to those with ILD who did not.
METHODS: In this retrospective cohort study, we identified adult, unvaccinated patients evaluated at the University of Chicago in 2020 who were enrolled in the ILD registry, and stratified by SARS-CoV-2 seropositive status. We then compared baseline clinical characteristics between SARS-CoV-2 seropositive and SARS-CoV-2 seronegative patients and assessed immunosuppressive therapy that the patient may have been on since ILD diagnosis. C-reactive protein and leukocyte subsets were evaluated at COVID diagnosis compared to the time of baseline ILD evaluation as were pulmonary function testing. Variable comparisons were determined by two-sided t-tests or chi-square tests as appropriate, and logistic regression models were fitted to assess the odds of death from COVID-19 using generalized linear models with maximum-likelihood estimation.
RESULTS: Of the 309 individuals with ILD in our cohort, 6.8% (n=21) tested positive for SARS-CoV-2. Those who were SARS-CoV-2 positive were younger (57 years vs 66 years; P=0.002), had baseline higher total lung capacity (81% vs 73%, P=0.045), similar forced vital capacity (71% vs. 67%, P=0.37), and similar diffusion capacity of carbon monoxide (71% vs. 62%, P=0.10) at baseline. Among patients with ILD and COVID-19, 67% had received immunosuppressive therapies compared to 74% of those with ILD without COVID-19. Those with ILD and COVID-19 were also more likely to have had a diagnosis of autoimmune-related ILD (connective tissue disease-ILD or interstitial pneumonia with autoimmune features) (62% vs 38%, P=0.029). Overall, the mortality hazard was highest among unvaccinated subjects with autoimmune-related ILD who had COVID-19 (OR=9.6, 95% CI=1.7-54.0; P=0.01).
CONCLUSIONS: SARS-CoV-2 is prevalent in ILD, and may put unvaccinated adults who are younger, with autoimmune ILD, and on immunosuppressive therapy at higher risk. This suggests a need for COVID-19 vaccinations and therapy (inpatient and outpatient) for this group of patients at high risk for COVID-19. Larger studies are needed to fully explore the relationship between ILD and immunosuppressive therapy in COVID-19.